The potential for intentional dissemination of naturally occurring infectious and toxic agents adds a serious new dimension to the threats traditionally posed by these agents. These bioterrorism threats have greatly increased our sense of urgency for developing defenses against Select Agent toxins. The Category B toxins, which consist of Clostridium perfringens epsilon toxin (ETX), ricin, and staphylococcal enterotoxin B (SEB), are all extraordinarily potent, and are derived from common, readily-accessible plants (ricin) and bacteria (SEB and ETX). These toxins are relatively easily produced, and can be delivered in a stable aerosol form -- their use as bioweapons on the battlefield or in civilian populations would result in devastating morbidity and mortality. There ae currently no preventives or therapeutics for exposure to these toxins. We have identified monoclonal antibodies (mAbs) that individually protect against lethal ETX, ricin, and SEB challenge in animal models. The goal of this application is development of a broad-spectrum antibody cocktail against the Category B toxins (CBT-ab), manufactured in a rapid and cost-effective plant system, for prevention and post-exposure treatment of intoxication. Pursuing a single product (the mAbs will be manufactured individually and then combined into the final product) against these three toxins will manifest as savings in costs and time. Further, a single cocktail product is desirable for clinical use since intoxication with the Category B toxins result in similar symptoms and point of care diagnostics to rapidly identify the causative agent are not generally available and/or accessible. The Specific Aims of this application are: Specific Aim #1. Evaluate CBT-ab in vitro and in vivo. The preventive and post-exposure activity of the cocktail will be demonstrated to satisfy requirements for submission of an Investigation New Drug (IND) application. Specific Aim #2. Identify a CBT-ab formulation. An optimal liquid formulation for the cocktail will be identified to ensure an appropriate stability profile for the final product. Speciic Aim #3. Complete IND-enabling studies. CBT-ab will be manufactured and formulated under current Good Manufacturing Practices (cGMP). All IND-enabling pharmacology, toxicology, and Chemistry, Manufacturing and Controls (CMC) studies will be performed, with a final goal of filing an Investigational New Drug (IND) application to support a Phase 1 human safety trial.